Studies will continue on the relationship of cyclic nucleotides to cell shape, adhesion and cell division. Three cell lines will be used which show different effects of exogenous CN on those endogenously generated. A general model for the regulation of the potentiality of microtubules to polymerize has been developed from other work in this laboratory. This involves regulation of the sulfhydrl-disulfide status of tubulin and its control by the glutathione regulatory system. Preliminary evidence suggests that this system works in cells in culture and this will be followed and its relation to CN explored. In addition, work is progressing on the mechanism of action of the antitumor agent maytansine which is also an antitubulin agent. We are studying the effects of this drug on intact cells, its competition with CN, its morphological effects, metabolism, etc. Suggestions have arisen that it is involved in some surface interactions involving tubulin.